帕金森氏症起因於中腦黑質體(substantianigra)的多巴胺神經元缺失，並顯示出肌肉僵直、震顫和行動障礙。針對帕金森氏症動物模型，體內多巴胺的電化學量測可提供監測多巴胺損耗之證據，但卻面臨腦中大量抗壞血酸(ascorbic acid)的干擾，因其同樣具有相似的電化學特性。在本研究中，我們提出: 1.利用金奈米粒子與自組裝單層膜進行修飾自行設計的微電極，以改善體內多巴胺量測的靈敏性和達到專一性排除抗壞血酸之干擾。2.為達到即時記錄大鼠腦部多巴胺濃度之效果，以安培法之原理研發微型化之電化學紀錄無線系統。
針對ω-mercaptoalkane carboxylic acid選擇最佳的烷基鏈長度，體外實驗顯示金奈米粒子和11-巰基十一酸(11-mercaptoundecanoic acid)修飾白金微電極對於多巴胺的檢測靈敏性的確大幅提升。藉由安培法的量測，11-巰基十一酸/金奈米粒子對抗壞血酸之抗干擾性有改善效果；此外，11-巰基十一酸/金奈米粒子具有許多的感測特性包括快速反應時間(少於2秒)、低檢測極限(100nM)、良好再現性之特點。並進一步對體外實驗進行系統驗證，以11-巰基十一酸/金奈米粒子的微電極，配合本自製系統可以偵測到在電位0.13伏特(以Ag/AgCl電極為參考電極)可觀察到一明顯峰電流，且伴隨連續多巴胺的添加可獲得成比例增加的趨勢。
為證實體內多巴胺量測的可行性，藉由施打多巴胺回收的抑制劑(nomifensine)加以誘發多巴胺釋放，而11-巰基十一酸/金奈米粒子修飾微電極已成功應用於麻醉大鼠紋狀體 (striatum)中，進行植入式檢測。
透過此實驗可證實所設計的微電極結合系統微小無線傳輸對於植入式、即時性監測多巴胺變化具有可行性，未來可應用於帕金森氏症的新穎治療模式，進行其療效之探討。此金奈米粒子/自組裝單層膜方法將延伸至對於SU-8基質所製備的可彎曲式感測電極進行表面改質，於帕金森氏症大鼠提供長期性的多巴胺量測，針對帕金森氏症病患管理而進行的各種治療，釐清其由皮質可塑性至多巴胺神經元之間所產生的調節性療效。

Parkinson’s disease (PD) is known to be caused by insufficient release of dopamine (DA). Recording the DA level of animal’s brain could provide a direct evidence for evaluating novel treatments for PD in the acute or long-term studies. However, detection of DA in the biological system with high selectivity and sensitivity has been great challenge in electroanalytical research. Thus, there is a great need to develop a novel electrochemical method to selectively detect DA in neural extracellular fluids of rat brain tissue especially during freely moving condition.
In order to improve the selectivity of DA sensing, this study of utilizesself-assembly monolayers (SAMs) for providing a simple and convenient method to functionalize the chemical properties of electrode-electrolyte interface. Suchalkanethiol compound constructs the negatively charged monolayers to provide the specific DA detection among competing L-ascorbic acid interferences. Moreover, the large sensing area of three-dimensional gold nanodendrite (Au-DT) is formed by electrodeposition, which possesses good sensitivity and faster electrons for real-time monitoring purposes for microelectrodes. Using amperometric i–t measurement, in vitro tests have shown that the responsive current of the platinum microelectrode coated with Au-DT and 11-mercaptoundecanoic acid (MUA) linearly depends on DA over the range of 0.1–1μM with a sensitivity of 0.377 nA/μM at fast response time of less than 2s.
Furthermore, the dopamine signal can be measured using amperometry technique which has been verified in acute animal model. The developed dopamine system can be transmitted in a wireless model which could be a useful experimental tool for continuous monitoring of dopamine levels for investigating PD treatment in freely moving rat.Our ultimate goal is to apply the wireless miniature DA sensing unit for in-vivo DA recording as a direct evidence and evaluation tool for novel treatment such as transcranial direct current stimulation (tDCS) treatment for PD animal study.

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